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Decay Pathway (decay + pathway)
Selected AbstractsHuman ATP-dependent RNA/DNA helicase hSuv3p interacts with the cofactor of survivin HBXIPFEBS JOURNAL, Issue 19 2005Michal Minczuk The human SUV3gene encodes an NTP-dependent DNA/RNA DExH box helicase predominantly localized in mitochondria. Its orthologue in yeast is a component of the mitochondrial degradosome complex involved in the mtRNA decay pathway. In contrast to this, the physiological function of human SUV3 remains to be elucidated. In this report we demonstrate that the hSuv3 protein interacts with HBXIP, previously identified as a cofactor of survivin in suppression of apoptosis and as a protein that binds the HBx protein encoded by the hepatitis B virus. Using deletion analysis we identified the region within the hSuv3 protein, which is responsible for binding to HBXIP. The HBXIP binding domain was found to be important for mitochondrial import and stability of the Suv3 protein in vivo. We discuss the possible involvement of the hSuv3p,HBXIP interaction in the survivin-dependent antiapoptotic pathway. [source] Inactivation of the decay pathway initiated at an internal site by RNase E promotes poly(A)-dependent degradation of the rpsO mRNA in Escherichia coliMOLECULAR MICROBIOLOGY, Issue 4 2003Paulo E. Marujo Summary In Escherichia coli, RNA degradation is mediated by endonucleolytic processes, frequently mediated by RNase E, and also by a poly(A)-dependent mechanism. The dominant pathway of decay of the rpsO transcripts is initiated by an RNase E cleavage occurring at a preferential site named M2. We demonstrate that mutations which prevent this cleavage slow down degradation by RNase E. All these mutations reduce the single-stranded character of nucleotides surrounding the cleavage site. Moreover, we identify two other cleavage sites which probably account for the slow RNase E-mediated degradation of the mutated mRNAs. Failure to stabilize the rpsO transcript by appending a 5, hairpin indicates that RNase E is not recruited by the 5, end of mRNA. The fact that nucleotide substitutions which prevent cleavage at M2 facilitate the poly(A)-dependent degradation of the rpsO transcripts suggest an interplay between the two mechanisms of decay. In the discussion, we speculate ,that ,a ,structural ,feature ,located ,in ,the ,vicinity of M2 could be an internal degradosome entry site promoting both RNase E cleavages and poly(A)-dependent degradation of the rpsO mRNA. We also discuss the role of poly(A)-dependent decay in mRNA metabolism. [source] Anthrax lethal toxin promotes dephosphorylation of TTP and formation of processing bodiesCELLULAR MICROBIOLOGY, Issue 4 2010Edith M. C. Chow Summary Anthrax lethal toxin (LeTx) is composed of protective antigen (PA) and lethal factor (LF) , PA is the receptor-binding moiety and LF is a protease that cleaves mitogen-activated protein kinase kinases (MAPKKs). LeTx subverts the immune response to Bacillus anthracis in several ways, such as downregulating interleukin-8 (IL-8) by increasing the rate of IL-8 mRNA degradation. Many transcripts are regulated through cis -acting elements that bind proteins that either impede or promote degradation. Some of these RNA-binding proteins are regulated by MAPKs and previous work has demonstrated that interfering with MAPK signalling decreases the half-life of IL-8 mRNA. Here, we have localized a segment within the IL-8 3, untranslated region responsible for LeTx-induced transcript destabilization and show that this is caused by inhibition of the p38, ERK and JNK pathways. TTP, an RNA-binding protein involved in IL-8 mRNA decay, became hypophosphorylated in LeTx-treated cells and knock-down of TTP prevented LeTx from destabilizing the IL-8 transcript. Cells that were treated with LeTx exhibited increased localization of TTP to Processing bodies, which are structures that accumulate transcripts targeted for degradation. We furthermore observed that LeTx promoted the formation of Processing bodies, revealing a link between the toxin and a major mRNA decay pathway. [source] Photophysical and Phototoxic Properties of the Antibacterial Fluoroquinolones Levofloxacin and MoxifloxacinCHEMISTRY & BIODIVERSITY, Issue 5 2004Giampietro Viola Two antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were investigated to evaluate their photophysical properties and to explore the mechanism of their phototoxicity. Photophysical experiments were carried out in aqueous solution by stationary and time-resolved fluorimetry, and by laser flash photolysis, to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. The results obtained show that levofloxacin is able to photosensitize red blood cell lysis in an oxygen-independent way and induce a high decrease in cell viability after UVA irradiation, although to a lesser degree than the racemic mixture ofloxacin. Moxifloxacin, which is an 8-MeO-substituted fluoroquinolone, is less phototoxic than the other compounds. Cellular phototoxicity was inhibited by the addition of superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion and/or a radical mechanism in their cytotoxicity. A good correlation was observed between lipid peroxidation, protein photodamage, and cellular phototoxicity, indicating that test compounds exert their toxic effects mainly in the cellular membrane. Experiments carried out on pBR322 DNA show that these derivatives do not significantly photocleave DNA directly, but single-strand breaks were evidenced after treatment of photosensitized DNA by two base-excision-repair enzymes, and Endo III. [source] | |||||||||||||